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5.
J Clin Invest ; 51(8): 2124-9, 1972 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-4403383

RESUMEN

Studies were performed in healthy volunteers to determine the effects of catecholamines and adrenergic-blocking agents on plasma and urinary levels of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP). Plasma cyclic AMP rose in response to infusions of the beta-adrenergic agent, isoproterenol, or in response to infusions of either epinephrine or norepinephrine alone or in combination with the alpha-adrenergic-blocking agent, phentolamine. Although urinary cyclic AMP also rose, the percentage increase was less than that observed in the plasma. These treatments caused no increase in plasma cyclic GMP. Plasma cyclic GMP rose in response to infusions of alpha-adrenergic agents, viz., epinephrine or norepinephrine infused together with the beta-blocking agent, propranolol. These treatments caused no increase in plasma cyclic AMP. These observations are consistent with the current concept that the actions of beta-adrenergic agents are mediated by increases in cyclic AMP formation in target tissues. Such a mediating role has not been established for cyclic GMP, but the data suggest the possibility that cyclic GMP metabolism is responsive either to alpha-adrenergic stimulation or to parasympathetic stimulation which occurs as a reflexive consequence of the pressor effect of alpha-adrenergic agents.


Asunto(s)
Catecolaminas/farmacología , AMP Cíclico , GMP Cíclico , Simpaticolíticos/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Antagonistas Adrenérgicos beta/farmacología , Adulto , Presión Sanguínea/efectos de los fármacos , AMP Cíclico/sangre , AMP Cíclico/orina , GMP Cíclico/sangre , GMP Cíclico/orina , Epinefrina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Isoproterenol/farmacología , Masculino , Norepinefrina/farmacología , Fentolamina/farmacología , Propranolol/farmacología
7.
J Clin Invest ; 49(12): 2222-36, 1970 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-5480849

RESUMEN

Kinetic parameters and the renal clearances of plasma adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) were evaluated in normal subjects using tritium-labeled cyclic nucleotides. Each tracer was administered both by single, rapid intravenous injection and by constant intravenous infusion, and the specific activities of the cyclic nucleotides in plasma and urine were determined. Both cyclic AMP and cyclic GMP were cleared from plasma by glomerular filtration. The kidney was found to add a variable quantity of endogenous cyclic AMP to the tubular urine, amounting to an average of approximately one-third of the total level of cyclic AMP excreted. Plasma was the source of virtually all of the cyclic GMP excreted. Plasma levels of the cyclic nucleotides appeared to be in dynamic steady state. The apparent volumes of distribution of both nucleotides exceeded extracellular fluid volume, averaging 27 and 38% of body weight for cyclic AMP and cyclic GMP, respectively. Plasma production rates ranged from 9 to 17 nmoles/min for cyclic AMP and from 7 to 13 nmoles/min for cyclic GMP. Plasma clearance rates averaged 668 ml/min for cyclic AMP and 855 ml/min for cyclic GMP. Approximately 85% of the elimination of the cyclic nucleotides from the circulation was due to extrarenal clearance.


Asunto(s)
Nucleótidos de Adenina/metabolismo , Nucleótidos de Guanina/metabolismo , Riñón/fisiología , Nucleótidos de Adenina/sangre , Nucleótidos de Adenina/orina , Cromatografía , Tasa de Filtración Glomerular , Nucleótidos de Guanina/sangre , Nucleótidos de Guanina/orina , Humanos , Inyecciones Intravenosas , Glomérulos Renales/fisiología , Túbulos Renales/fisiología , Cinética , Unión Proteica , Tritio
8.
J Clin Invest ; 49(12): 2237-45, 1970 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-5480850

RESUMEN

Glucagon, infused intravenously into fasting, well-hydrated, normal men in doses of 25-200 ng/kg per min, induced up to 30-fold increases in both plasma and urinary cyclic AMP. Cyclic GMP levels were unaffected by glucagon. Simultaneous cyclic AMP and inulin clearance studies demonstrated that the glucagon-induced increase in urinary cyclic AMP was entirely due to glomerular filtration of the elevated plasma levels of the nucleotide. The cyclic AMP response to glucagon was not mediated by parathyroid hormone or epinephrine, and trypsintreated glucagon was completely inactive. The perfused rat liver released cyclic AMP into the perfusate in response to glucagon, indicating that the liver is a possible source of the cyclic AMP entering the extracellular fluids in response to glucagon in vivo.


Asunto(s)
Nucleótidos de Adenina/metabolismo , Glucagón/farmacología , Nucleótidos de Guanina/metabolismo , Nucleótidos de Adenina/sangre , Nucleótidos de Adenina/orina , Adulto , Epinefrina/farmacología , Ayuno , Glucosa/farmacología , Nucleótidos de Guanina/sangre , Nucleótidos de Guanina/orina , Humanos , Inyecciones Intravenosas , Insulina/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Hormona Paratiroidea/farmacología , Perfusión , Tripsina/farmacología , Inhibidores de Tripsina/farmacología
9.
J Clin Invest ; 49(12): 2387-95, 1970 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-5480862

RESUMEN

The effects of parathyroid hormone (PTH) on plasma and urinary adenosine 3',5'-monophosphate (cyclic AMP) levels were studied in normal subjects. Under basal conditions normal adults have plasma concentrations of cyclic AMP ranging from 10 to 25 nmoles/liter and excrete from 1.5 to 5 mumoles of cyclic AMP per g of urinary creatinine. About one-half to two-thirds of the cyclic AMP excreted in the urine is derived from the plasma by glomerular filtration, and the remainder is produced by the kidney. Renal production of cyclic AMP is partly under the control of PTH. It can be suppressed by infusions of calcium and stimulated by infusions of the calcium chelating agent, EDTA. Infusions of PTH in doses up to 10 mU/kg per min were associated with dose-related increases both in urinary cyclic AMP and phosphate. Infusions of PTH in doses ranging from 20 to 80 mU/kg per min did not lead to any further increase in phosphaturia but did lead to further marked increases in urinary cyclic AMP. A modest increase in plasma cyclic AMP was noted when PTH was infused at 40 mU/kg per min. Anephric patients failed to show appreciable increases in plasma cyclic AMP in response to large doses of PTH but did show expected increases in response to glucagon. Surgical removal of parathyroid adenomas from nine patients with primary hyperparathyroidism was invariably followed by a decrease in urinary cyclic AMP, PTH, in large doses, and calcium infusion produced up to 2-fold increases in the other known naturally occurring cyclic nucleotide, guanosine 3',5'-monophosphate (cyclic GMP).


Asunto(s)
Nucleótidos de Adenina/sangre , Nucleótidos de Adenina/orina , Hormona Paratiroidea/farmacología , Adulto , Calcio/farmacología , Tasa de Filtración Glomerular , Glucagón/farmacología , Nucleótidos de Guanina/orina , Humanos , Hiperparatiroidismo/metabolismo , Hipocalcemia/metabolismo , Inyecciones Intravenosas , Riñón/metabolismo , Masculino , Hormona Paratiroidea/metabolismo
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